Autophagy is an important physiological process that can degrade cellular components and maintain cellular homeostasis. In the process of cancer development, autophagy plays a dual role in promoting or inhibiting autophagy, and targeting autophagy is considered to be an important means of cancer treatment. According to Chinese medicine theory, autophagy has the function of regulating the balance of Yin and Yang, and the balance of good and evil in the organism, and based on the theory of "supporting the positive and dispelling the evil", the use of active ingredients of traditional Chinese medicine (TCM) to target autophagy has been proven to be effective in the treatment of cancer. In addition, autophagic cell death, as a type Ⅱ programmed cell death, is often accompanied by autophagic features, and the regulation of autophagic cell death is an important way for autophagy to achieve anti-tumor effects. In recent years, more and more studies have found that the active ingredients of TCM have good effects in cancer treatment, among which, targeting autophagic cell death is an important way for TCM active ingredients to achieve anti-tumor effects. This paper outlines the understanding of cancer and autophagy in Chinese medicine theory, and summarizes the current Chinese medicine small molecule compounds targeting autophagic cell death and their mechanisms of action based on the classification of natural medicines. Finally, the development of Chinese medicine-derived compounds targeting autophagic cell death for the treatment of diseases is summarized and prospected, which hopefully can provide clues for subsequent exploration and research.

Tumor immunotherapy represented by blocking programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) has gained better therapeutic effect in lung cancer treatment, and the development of small molecule drugs to block PD-1/PD-L1 provides a new strategy for lung cancer immunotherapy. In this study, we applied an in vitro cell model to investigate the regulation of PD-L1 expression and the mechanism of action of baicalin on A549 lung cancer cells. The effects of baicalin on the viability of A549 cells were detected by CCK8 assay; the expression of PD-L1 protein in A549 cells was detected by Western blot; the mechanism of baicalin cytotoxicity and its correlation with PD-L1 protein expression were investigated by using small-molecule inhibitors of apoptosis and autophagy; the formation of autophagic vesicles in A549 cells treated with baicalin was observed under transmission electron microscope. And the alterations of acid autophagic vesicles and autophagic lysosomes were observed under fluorescence microscope. The results of CCK8 experiments showed that baicalin (12.5-400 μmol·L^-1) inhibited the proliferation of A549 cells in a dose-dependent manner; at the same time, the elevation of PD-L1 protein expression after interferon-γ (IFN-γ) interference could be reduced with the increase of baicalin concentration; on the other hand, treatment with autophagy inhibitors, wortmannin, and chloroquine, could call back the baicalin-induced cytotoxicity, transmission electron microscopy and fluorescence microscopy showed that the number of autophagic vesicles increased after baicalin treatment of A549 cells, and Western blot results showed that baicalin promoted the expression of autophagy-related proteins LC3-Ⅱ/Ⅰ and beclin-1; the number of baicalin-induced acidic autophagic vesicles in A549 cells was attenuated after the intervention of wortmannin, and at the same time the LC3-Ⅱ/Ⅰ expression was inhibited and the inhibitory effect on PD-L1 was regulated. The above results suggest that baicalin may exert antitumor effects by activating the autophagy protein LC3 in A549 cells to reduce the expression of PD-L1. This study lays the foundation for baicalin to have the ability to be developed as a small molecule blocker of the PD-1/PD-L1 signaling pathway.

Resiquimod (R848) belongs to the class of weak base organic compounds that are derivatives of imidazole quinoline and is a potent agonist of Toll-like receptor (TLR) 7/8. R848 can be considered an effective immune adjuvant as it has the ability to activate different immune cells and regulate innate and adaptive immunity. A number of researches done recently have reported R848 potent anti-tumor capacity, especially when combined with other cytotoxic therapies. Nonetheless, some hurdles remain with the clinical use of R848 such as its limited ability to reach the tumor and likelihood of inflammation and autoimmune responses which might result from repeated delivery of high dosages of the drug. Nanoscale drug delivery systems may overcome some of these challenges. Various nanoformulations, including liposomes, polymeric nanoparticles, biocarriers, inclusion compound, metal-organic frameworks and inorganic nanoparticles, as well as several R848 prodrugs or derivatives-baesd nanoparticles, have been incorporated into present R848 delivery platforms. This article reviews the physicochemical properties, immune regulatory mechanisms and nano drug delivery systems of R848, in order to provide reference and support for anti-tumor research and new drug development.

Prenylated aromatic natural products (PANPs) are widely distributed in nature. PANPs exhibit a great structural diversity due to their various core scaffolds (coumarin, lignan, benzoic acid/benzyl alcohol, flavonoid, xanthone, anthraquinone, and aromatic alkaloid, etc.) and the distinct types and substitution sites of isoprenoid moieties which may possess either linear or cyclic structures. The structural diversity of PANPs endow them with various bioactivities including anti-bacterial, anti-oxidation, anti-cancer, anti-inflammatory and analgesic effects, which makes them a group of highly promising molecules for drug development. Notably, isoprenoid moieties are often the indispensable pharmacophores in these active PANPs. Aromatic prenyltransferases (aPTs) are responsible for prenylation in the biosynthesis of PANPs. aPTs can be divided into three classes according to their evolutionary relationships and structural features, i.e. membrane-bound aPTs (UbiA type), soluble aPTs with a PT barrel structure (ABBA type and DMATS type) and terpene synthase-like aPTs. Herein, we summarize 94 aPTs belonging to the different classes which were characterized in the past ten years, in particular introduce their substrate selectivity/tolerance, regioselectivity, evolutionary relationships and structural features. This would provide cues for discovery and engineering of new aPTs, and modification and bio-production of active PANPs.

The study investigates the therapeutic effects and mechanisms of Buyang Huanwu Decoction (BHD) in treating ischemic stroke (IS). Using a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model, we evaluated the neuroprotective effects of BHD, demonstrating significant improvements in neurological function scores, prolonged rotarod retention time, and reductions in both infarct volume and brain water content. An unsupervised clustering algorithm was employed to identify active components of BHD by clustering them with FDA-approved drugs for ischemic stroke treatment. Combined with network pharmacology analysis, the mechanisms of these active components were predicted to be associated with anti-inflammatory pathways. Further validation using a lipopolysaccharide (LPS)-induced BV-2 cell model demonstrated the anti-inflammatory efficacy of seven key active components, with their effects on anti-inflammatory activity and cell viability assessed via the Griess and MTT assays. Additionally, the content of these active components in BHD was quantified using liquid chromatography-mass spectrometry (LC-MS). In conclusion, this study elucidates the critical active components of BHD and their potential pharmacological mechanisms, providing valuable insights for the modernization of traditional Chinese medicine and its application in ischemic stroke therapy. All animal experiments were approved by the Animal and Medical Ethics Committee of Northeastern University (approval No.: NEU-EC-2023A052S).

This study aimed to clarify the mechanism and active components of Buyang Huanwu Decoction (BYHWD) in alleviating cerebral ischemia reperfusion injury (CIRI) by inhibiting pyroptosis. The key components and targets of BYHWD for CIRI were identified via network pharmacological analysis, followed by molecular docking performed with Autodock and Pymol software. The effects of BYHWD and its active components were validated in vivo and in vitro. A middle cerebral artery occlusion (MCAO) model was established in mouse to assess neural function alterations in mice under various conditions. Concurrently, an oxygen-glucose deprivation/reperfusion (OGD/R) model was developed utilizing mouse brain tissue astrocytes in vitro. Molecular biology experiments were used to verify the predicted key targets. We have determined that the principal components of BYHWD are baicalein and β-sitosterol. By analyzing genes associated with CIRI pathology alongside those linked to pyroptosis, 20 intersecting genes were identified. In conjunction with molecular docking binding energy assessment, TP53 and TNF emerged as pivotal core targets for subsequent validation. Molecular biology experiments confirmed that BYHWD effectively alleviates injury while reducing the expression level of P53. These findings indicate that the primary bioactive constituents of BYHWD were baicalein and β-sitosterol. In addition, BYHWD may inhibit pyroptosis via TNF and TP53 in protecting CIRI. The experiment has been approved by the Experimental Animal Welfare Ethics Committee of Zhejiang Academy of Traditional Chinese Medicine, approval number (KTSC2020037, KTSC2023030).

Non-small cell lung cancer (NSCLC) is the primary pathological type of lung cancer. Osimertinib, as a third-generation EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) targeted drug, effectively prolong the progression-free survival of patients with EGFR-mutated NSCLC. However, drug resistance limits the efficacy of osimertinib. Traditional Chinese medicine can effectively delay the resistance to EGFR-TKIs. In this study, Cucurbitacin B (CuB) was investigated to analyze its pharmacological effects in osimertinib-resistant NSCLC cells through cell viability, migration, and invasion experiments. Public databases were used to screen potential targets of CuB in osimertinib-resistant NSCLC cells, and the interactions between CuB and potential targets were verified through molecular docking, cellular thermal shift assay (CETSA), and microscale thermophoresis (MST). Western blot was used to detect the effects of CuB on downstream pathways of the targets. The results showed that CuB significantly reduced the proliferation activity of osimertinib-resistant NSCLC cells and inhibited the migration and invasion abilities of tumor cells. Mechanistically, CuB inhibited the expression of ERK and AKT molecules by binding to the tyrosine kinase receptor AXL. In summary, CuB exhibits resistance to osimertinib-resistant NSCLC by inhibiting the migration and invasion of resistant cells through regulating the abnormal activation of the AXL-ERK/AKT axis. This study provides a basis for the pre-clinical in vitro efficacy of CuB in the treatment of osimertinib targeted resistance in NSCLC and theoretical support for the development of clinical drug combinations.

Platinum-based complexes, particularly divalent platinum [platinum(Ⅱ), Pt(Ⅱ)] compounds, have become classic chemotherapy agents for the treatment of malignant tumors. However, their widespread clinical use is limited due to issues such as insufficient stability, the induction of acquired resistance and strong cytotoxicity. Although antibodies that interfere with the interaction between programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1), in combination with platinum-based compounds, have shown significant clinical progress in cancer treatment, their high efficacy is often accompanied by substantial toxicity and immune-related side effects, which limit their long-term use. In contrast, platinum(Ⅳ) [Pt(Ⅳ)] complexes, with their unique octahedral geometry, have demonstrated promising anticancer potential. By modifying the axial ligands, Pt(Ⅳ)-based complexes not only show higher inertness and improved tumor selectivity, but also enable the targeted release of active ligands in the tumor microenvironment. The mechanism allows Pt(Ⅳ)-based complexes to overcome drug resistance, reduce toxicity and enhance immune system activation, making them a research hotspot in the current cancer field. More importantly, Pt(Ⅳ)-based complexes can exert anticancer effects through multiple pathways including causing DNA damage to trigger apoptosis, autophagy and ferroptosis in tumor cells. This multifaceted action mechanism not only enhances antitumor efficacy but also significantly reduces side effects associated with traditional platinum-based compounds. This review summarizes whole anticancer mechanisms of platinum-based complexes, particularly Pt(Ⅳ) complexes in chemo-immunetherapy combination therapies, discussing their potential in cancer treatment and providing theoretical support for the development of efficient, low-toxicity and highly selective Pt(Ⅳ)-based complexes.

This study mainly explored the anti-tumor effects of programmed death ligand 1/ transforming growth factor-β (PD-L1/TGF-β) bispecific antibody drugs in the huHSC-NCG mouse brain orthotopic transplantation model of human glioma cell U251-luciferase (all animal experiments in this study were approved by the Experimental Animal Ethics Committee of GemPharmatech, and the ethics review number is GPTAP20230706-3). The antibody-antigen binding activity of the PD-L1/TGF-β bispecific antibody drugs to PD-L1 target on U251 cells was detected by flow cytometry in vitro. The antitumor activity of PD-L1/TGF-β bispecific antibody drugs was evaluated using a brain glioma in orthotopic implantation model with humanized immune system. Live animal imaging and brain tissue (including tumor tissue) weight results showed that the PD-L1/TGF-β dual antibody drug had an inhibitory effect on the growth of glioma in situ. The results of drug content (ELISA assay) and drug distribution (immunohistochemistry assay) in brain tissue showed that PD-L1/TGF-β dual antibody could enter the brain glioma and play the function of immune checkpoint, thus playing an inhibitory role in brain glioma. Immunofluorescence staining of mouse brain tissue showed that the drug activated the immune system and had synergistic anti-tumor effect with the immune system. These results showed that the PD-L1/TGF-β bispecific antibody drugs have broken through the blood-tumor barrier in orthotopic implantation model of mouse brain glioma and demonstrated a strong anti-tumor effect. In conclusion, the inhibitory effects of PD-L1/TGF-β bispecific antibody drugs on human brain glioma provides a new strategy for the treatment of human brain glioma.

Wound healing caused by skin trauma and chronic diseases is often complicated and difficult due to infection. In such cases, the wound healing process is not only a long and continuous one, but also prone to scar repair. Conventional dressings and antibiotic treatments suffer from issues such as low drug delivery efficiency and systemic toxicity. In recent years, microneedle technology has been widely used to reduce infection and promote wound healing. Microneedles can not only penetrate the skin stratum corneum and biofilm to enhance drug delivery efficiency and reduce drug side effects, but also can be combined with a variety of materials to achieve multiple treatments and monitoring of wounds. This article will discuss the healing mechanism of infected wounds, the classification of microneedles, and their applications in the treatment of infected wounds.